A protein family of STAT (signal transducers and activators of transcription) is one of a DNA binding protein and plays a role in information transmission and transcription activation. At present, the STAT family is known to have 6 different members (STAT 1, STAT 2, STAT 3, STAT 4, STAT 5 and STAT 6) and several iso-forms (STAT 1α, STAT 1β, STAT 3α, STAT3β, STAT 5a and STAT 5b). The activity of STAT is regulated by stimulation of various cytokines and mitogen. When a cytokine binds to its receptors, Janus protein tyrosine kinase (JAK) associated with the receptors is activated.
STAT 3 has a SH2 (src homology 2) domain capable of recognizing the structure of a specifically phosphorylated tyrosine. It is considered that STAT 3 specifically recognizes the phosphorylated tyrosine within a gp130 cell region and is conveyed onto gp 130 and tyrosine is phosphorylated by JAK. STAT 3 having phosphorylated tyrosine forms a STAT 3 dimer (homodimer) via its SH2 domain or a dimer (heterodimer) of STAT 3 and STAT1, which moves into a nucleus, and recognizes a specific DNA sequence and binds it. In this way, STAT3 is known to regulate transcription of many genes.
Such in-vivo roles of STAT3/5 are reported in several documents.
For example, Non-Patent Document 1 describes the relationships between activation of STAT 3 and IL-6-signaling pathways and between IL-6 and chronic diseases such as Alzheimer's disease, rheumatism, Crohn disease and anemia and cancer associated disease such as cachexia.
Furthermore, Non-Patent Document 2 describes the relationship between STAT 3 activation and Hepatitis C Virus, Non-Patent Document 3 describes the relationship between STAT 3 activation and psoriasis, individually. Moreover, Non-Patent Document 2 sets forth the relationships between STAT 3 and an inflammatory disease and an autoimmune disease, and Non-Patent Document 4 sets forth the relationships between STAT 3 activation and obesity, diabetes, infertility, and thermal dysregulaton, etc., individually. Non-Patent Documents 5 and 6, etc. describe that STATS is a critical factor in IgE-induced MC (mast cell) activation, and inflammatory and autoimmune diseases, and describe STATS's roles in allergies, inflammations, hyperprolactinemia, and malignant tumors.
On the other hand, it is known that an aromatic compound having a collagen production inhibitory action is present (Patent Document 1). However, it has been not yet known that the aromatic compound described in Patent Document 1 has a STATS/5 activation inhibitory action.    [Patent Document 1] WO2006/014012    [Patent Document 2] US2001/0029250    [Non-Patent Document 1] J. Gerontology; MEDICAL SCIENCES 2006, Vol. 61A, No. 6, 575-584    [Non-Patent Document 2] J. Exp. Med. Vol. 196, No. 5, 2002, 641-653    [Non-Patent Document 3] Nature Medicine Vol. 11, No. 1, 2005, 43-49    [Non-Patent Document 4] PNAS Mar. 30, 2004, vol. 101, no. 13, 4661-4666    [Non-Patent Document 5] J. Immunology, 2006, 177: 3421-3426,    [Non-Patent Document 6] Ann. Rheum. Dis. 2004; 63: 67-71